Formaldehyde derived from dietary aspartame binds to tissue components in vivo

Life Sci. 1998;63(5):337-49. doi: 10.1016/s0024-3205(98)00282-3.


Adult male rats were given an oral dose of 10 mg/kg aspartame 14C-labelled in the methanol carbon. At timed intervals of up to 6 hours, the radioactivity in plasma and several organs was investigated. Most of the radioactivity found (>98% in plasma, >75% in liver) was bound to protein. Label present in liver, plasma and kidney was in the range of 1-2% of total radioactivity administered per g or mL, changing little with time. Other organs (brown and white adipose tissues, muscle, brain, cornea and retina) contained levels of label in the range of 1/12 to 1/10th of that of liver. In all, the rat retained, 6 hours after administration about 5% of the label, half of it in the liver. The specific radioactivity of tissue protein, RNA and DNA was quite uniform. The protein label was concentrated in amino acids, different from methionine, and largely coincident with the result of protein exposure to labelled formaldehyde. DNA radioactivity was essentially in a single different adduct base, different from the normal bases present in DNA. The nature of the tissue label accumulated was, thus, a direct consequence of formaldehyde binding to tissue structures. The administration of labelled aspartame to a group of cirrhotic rats resulted in comparable label retention by tissue components, which suggests that liver function (or its defect) has little effect on formaldehyde formation from aspartame and binding to biological components. The chronic treatment of a series of rats with 200 mg/kg of non-labelled aspartame during 10 days resulted in the accumulation of even more label when given the radioactive bolus, suggesting that the amount of formaldehyde adducts coming from aspartame in tissue proteins and nucleic acids may be cumulative. It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Aspartame / metabolism*
  • Aspartame / toxicity
  • Carbon Radioisotopes
  • Chromatography, Thin Layer
  • DNA Adducts / metabolism
  • Formaldehyde / chemistry
  • Formaldehyde / metabolism*
  • Kidney / metabolism*
  • Liver / metabolism*
  • Liver Cirrhosis, Experimental / metabolism
  • Male
  • Methanol / metabolism
  • Protein Binding
  • Rats
  • Rats, Wistar


  • Carbon Radioisotopes
  • DNA Adducts
  • Formaldehyde
  • Methanol
  • Aspartame